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Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma

机译：单细胞RNA-seq突出原发性胶质母细胞瘤的肿瘤内异质性

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摘要

Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells from five primary glioblastomas, which we found to be inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. We also observed a continuum of sternness-related expression states that enabled us to identify putative regulators of sternness in vivo. Finally, we show that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor and demonstrate the potential prognostic implications of such intratumoral heterogeneity. Thus, we reveal previously unappreciated heterogeneity in diverse regulatory programs central to glioblastoma biology, prognosis, and therapy.
机译：人类癌症是由具有不同表型，基因型和表观遗传状态的细胞组成的复杂生态系统，但是当前的模型不能充分反映患者的肿瘤组成。我们使用单细胞RNA测序（RNA-seq）对来自五个原发性胶质母细胞瘤的430个细胞进行了分析，我们发现它们在与致癌信号，增殖，补体/免疫反应和缺氧有关的多种转录程序的表达中具有固有的可变性。我们还观察到了严密相关表达状态的连续性，这使我们能够确定体内严谨性的假定调节因子。最后，我们显示已建立的胶质母细胞瘤亚型分类器在肿瘤内的各个细胞中可变表达，并证明了这种肿瘤内异质性的潜在预后意义。因此，我们揭示了胶质母细胞瘤生物学，预后和治疗的各种调节方案中以前未曾意识到的异质性。

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  • 来源
    《Science》 |2014年第6190期|1396-1401|共6页
  • 作者

    Anoop P. Patel; Itay Tirosh; John J. Trombetta; Alex K. Shalek; Shawn M. Gillespie; Hiroaki Wakimoto; Daniel P. Cahffl; Brian V. Nahed; William T. Curry; Robert L. Martuza; David N. Louis; Orit Rozenblatt-Rosen; Mario L. Suva; Aviv Regev; Bradley E. Bernstein;

  • 作者单位

    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,USA,Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA,Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA,Howard Hughes Medical Institute Chevy Chase, MD 20815, USA;

    Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA;

    Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA;

    Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA;

    Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA,Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA,Howard Hughes Medical Institute Chevy Chase, MD 20815, USA;

    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,USA;

    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,USA;

    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,USA;

    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,USA;

    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,USA;

    Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;

    Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA;

    Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA,Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA;

    Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA,Howard Hughes Medical Institute Chevy Chase, MD 20815, USA,Department of Biology, MIT, Cambridge, MA 02139, USA;

    Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA,Broad Institute of Harvard and Massachusetts Institute of Techonology (MIT),Cambridge, MA 02142, USA,Howard Hughes Medical Institute Chevy Chase, MD 20815, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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  • 入库时间 2022-08-18 02:52:27

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